The Laser Microbeam and Medical Program (LAMMP) is an NIH Biotechnology Resource Center dedicated to the user of lasers and optics in biology and medicine. LAMMP is located within the Beckman Laser Institute and Medical Clinic (BLIMC), an interdisciplinary biomedical research, teaching, and clinical facility at the University of California, Irvine. Overall resource objectives are to promote a well-balanced Center with activities in technological research and development, collaborative/service research, and training dissemination. An additional unique feature of LAMMP is the ability to facilitate "translational" research by rapidly implementing novel basic science discoveries in a clinical setting. In the fourth renewal of this Resource, we propose to consolidate LAMMP technology development by establishing Core Research Programs spanning three fundamental regimes of light-tissue interaction: 1) High Intensity Interactions, 2) Coherent Interactions, and 3) Diffuse Interactions. We will use insight gained from each of these core programmatic research areas to develop novel LAMMP technologies (i.e. instrumentation, techniques and models) specifically for enhancing our understanding of how high intensity, coherent, and diffuse radiation interacts with and propagates through cells and tissues. These technologies are specifically designed to visualize and manipulate physiology in cells/tissues. Applications will enable us to generate fundamental information that uniquely contributes to solving important biological problems. The overall scientific impact of LAMMP will be amplified by engaging in a broad range of collaborative projects and providing training/dissemination for students, postdoctoral/medical fellows, and the outside research community. These activities will: 1) strongly couple of optical/engineering expertise of LAMMP with mainstream activities in cellular/molecular biology and biophysics; 2) enhance cross-disciplinary approaches to solving important biological and biomedical problems; and, 3) facilitate rapid, efficient technology transfer to academic laboratories and, where appropriate, industry.